MACC1 Suppresses Cell Apoptosis in Hepatocellular Carcinoma by Targeting the HGF/c-MET/AKT Pathway

Yao, Yingmin; Dou, Chanwei; Lu, Zhongxin; Zheng, Xin; Liu, Qingguang

doi:10.1159/000369754

Cited by 48 publications

(50 citation statements)

References 21 publications

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“…MACC1, first identified as a colon cancer oncogene, potentially functions as an early diagnosis biomarker and is associated with the progression of multiple solid tumors (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Stein et al (12) demonstrated that MACC1 upregulation was associated with benign-malignant tumor transition.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, previous studies have revealed that the abnormal expression of MACC1 may be associated with the development and progression of numerous types of solid tumor, including lung (13,14) and gastric cancer (15)(16)(17)(18), hepatocellular carcinoma (19)(20)(21), breast cancer (22), glioma (23) and colon (12,24) and esophageal cancer (25). These studies suggested that MACC1 may serve as a key biomarker for recurrence, metastasis and patient survival in multiple types of human cancer.…”

Section: Introductionmentioning

confidence: 94%

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Downregulation of MACC1 inhibits the viability, invasion and migration and induces apoptosis in esophageal carcinoma cells through the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B signaling pathway

Qian

Xia-qin²,

et al. 2017

Oncology Letters

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Abstract.As an oncogene, MACC1 serves an important function in cancer progression and metastasis. However, the effect of MACC1 in esophageal carcinoma (EC) remains to be fully understood. The present study assessed the association between MACC1 expression and the progression of EC cells. A small interfering (si)RNA was delivered into EC cells to downregulate MACC1 expression. The MTT assay demonstrated that EC cell viability was reduced by siRNA-MACC1. Decreasing MACC1 expression increased the apoptotic rate of EC cells compared with control cells. Transwell and Matrigel assays demonstrated that EC cell migration and invasion, respectively, were downregulated by siRNA-MACC1. Furthermore, knocking down MACC1 suppressed the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway by upregulating the expression of phosphatase and tensin homolog (PTEN), a tumor suppressor. The results of the present study revealed that MACC1 expression affected cellular functions of the EC cells through the PTEN/PI3K/Akt signaling pathway. Therefore, MACC1 may potentially serve as a novel biomarker and therapeutic target for EC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Downregulation of MACC1 inhibits the viability, invasion and migration and induces apoptosis in esophageal carcinoma cells through the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B signaling pathway

Qian

Xia-qin²,

et al. 2017

Oncology Letters

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show abstract

“…Total RNA from cells was isolated using the Trizol reagent (Invitrogen, USA) according to the manufacturer's instruction as described previously [17]. Reverse transcript (RT) was carried out with the SuperScript First-Strand Synthesis System for RT-PCR (Invitrogen, USA), and quantitative real-time PCR was carried out using the SYBR Green reporter.…”

Section: Quantitative Real-time Pcr (Qrt-pcr) Assaymentioning

confidence: 99%

Forkhead Box Protein C2 Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in Cisplatin-Resistant Human Ovarian Cancer Cell Line (SKOV3/CDDP)

Ding

Tian

et al. 2016

Cell Physiol Biochem

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Background/Aims: Forkhead Box Protein C2 (FOXC2) has been reported to be overexpressed in a variety of human cancers. However, it is unclear whether FOXC2 regulates epithelial-mesenchymal transition (EMT) in CDDP-resistant ovarian cancer cells. The aim of this study is to investigate the effects of FOXC2 on EMT and invasive characteristics of CDDP-resistant ovarian cancer cells and the underlying molecular mechanism. Methods: MTT, Western blot, scratch wound healing, matrigel transwell invasion, attachment and detachment assays were performed to detect half maximal inhibitory concentration (IC₅₀) of CDDP, expression of EMT-related proteins and invasive characteristics in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) and its parental cell line (SKOV3). Small hairpin RNA (shRNA) was used to knockdown FOXC2 and analyze the effect of FOXC2 knockdown on EMT and invasive characteristics of SKOV3/CDDP cells. Also, the effect of FOXC2 upregulation on EMT and invasive characteristics of SKOV3 cells was analyzed. Furthermore, the molecular mechanism underlying FOXC2-regulating EMT in ovarian cancer cells was determined. Results: Compared with parental SKOV3 cell line, SKOV3/CDDP showed higher IC₅₀ of CDDP (43.26μM) (P<0.01) and acquired EMT phenotype and invasive characteristics. Gain- and loss-of-function assays indicated that shRNA-mediated FOXC2 knockdown could reverse EMT and reduce the capacity of migration, invasion, attachment and detachment in SKOV3/CDDP cell line and upregulation of FOXC2 could induce the reverse effects in parental SKOV3 cell line. Furthermore, it was found that activation of ERK or AKT/GSK-3β signaling pathways was involved in FOXC2-promoting EMT in CDDP-resistant ovarian cancer cells. Conclusions: Taken together, these data demonstrate that FOXC2 may be a promoter of EMT phenotype in CDDP-resistant ovarian cancer cells and a potential therapeutic target for the treatment of advanced ovarian cancer.

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“…Thus, the mitochondrial apoptotic events play an important role in PI3K inhibitor-mediated sensitization for apoptosis [18-20]. …”

Section: Introductionmentioning

confidence: 99%

Alpha1-ACT Functions as a Tumour Suppressor in Hepatocellular Carcinoma by Inhibiting the PI3K/AKT/mTOR Signalling Pathway via Activation of PTEN

Zhu¹,

Liu²,

Tang³

et al. 2017

Cell Physiol Biochem

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Background & Aims: To investigate the expression and prognostic value of α1-ACT (Alpha1-antichymotrypsin) in patients with HCC (hepatocellular carcinoma) and identify the mechanism by which α1-ACT inhibits proliferation and promotes apoptosis of HCC. Methods: We first measured α1-ACT expression levels and determined their relationship with the clinicopathological characteristics and prognosis of patients with HCC.We then established stable HCC cell lines with both α1-ACT overexpression and knockdown and performed a functional analysis in vitro.We first examined the relationship between α1-ACT and the PTEN/PI3K/AKT/mTOR pathway using Western blotting. Then, we determined whether α1-ACT can directly bind to PTEN using co-immunoprecipitation. Finally, we measured α1-ACT expression to evaluate its correlation with the PI3K/AKT/mTOR pathway-related apoptosis proteins in a xenograft tumour mouse model using immunohistochemistry. Results: The α1-ACT expression level was significantly lower in the HCC tissues than in the paratumour tissues and was negatively positively correlated with the level of Ki67, AFP, the AJCC stage, tumour size and tumour invasion. The overexpression of α1-ACT can inhibit cell proliferation and increase cell apoptosis by activating PI3K/AKT/mTOR-mediated apoptosis via binding to PTEN and activating it in vitro. Additionally, the overexpression of α1-ACT can also increase the proportion of cells in the G0/G1 stage by increasing cyclin p21 expression and inhibiting the migration and invasion abilities of HCC cells by regulating MMP2 and MMP9. The xenotransplantation studies with nude mice also showed that overexpression of α1-ACT inhibited tumourigenesis and knockdown of α1-ACT had the opposite effect. Conclusions: Our study demonstrates that α1-ACT suppresses liver cancer development and metastasis via targeting the PTEN/PI3K/AKT/mTOR signalling pathway, which may be a potential target for therapeutic intervention in HCC.

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MACC1 Suppresses Cell Apoptosis in Hepatocellular Carcinoma by Targeting the HGF/c-MET/AKT Pathway

Cited by 48 publications

References 21 publications

Downregulation of MACC1 inhibits the viability, invasion and migration and induces apoptosis in esophageal carcinoma cells through the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B signaling pathway

Downregulation of MACC1 inhibits the viability, invasion and migration and induces apoptosis in esophageal carcinoma cells through the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B signaling pathway

Forkhead Box Protein C2 Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in Cisplatin-Resistant Human Ovarian Cancer Cell Line (SKOV3/CDDP)

Alpha1-ACT Functions as a Tumour Suppressor in Hepatocellular Carcinoma by Inhibiting the PI3K/AKT/mTOR Signalling Pathway via Activation of PTEN

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